scholarly journals High Prevalence of Hypervirulent Klebsiella pneumoniae Infection in China: Geographic Distribution, Clinical Characteristics, and Antimicrobial Resistance

2016 ◽  
Vol 60 (10) ◽  
pp. 6115-6120 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Geographic Distribution ◽  
Virulence Gene ◽  
Bloodstream Infections ◽  
Systemic Steroid ◽  
Content Type ◽  
Invasive Infections ◽  
Clinical Awareness ◽  
Abdominal Infections

ABSTRACTHypervirulentKlebsiella pneumoniae(hvKP) is traditionally defined by hypermucoviscosity, but data based on genetic background are limited. Antimicrobial-resistant hvKP has been increasingly reported but has not yet been systematically studied.K. pneumoniaeisolates from bloodstream infections, hospital-acquired pneumonia, and intra-abdominal infections were collected from 10 cities in China during February to July 2013. Clinical data were collected from medical records. AllK. pneumoniaeisolates were investigated by antimicrobial susceptibility testing, string test, extended-spectrum β-lactamase (ESBL) gene detection, capsular serotypes, virulence gene profiles, and multilocus sequence typing. hvKP was defined by aerobactin detection. Of 230K. pneumoniaeisolates, 37.8% were hvKP. The prevalence of hvKP varied among different cities, with the highest rate in Wuhan (73.9%) and the lowest in Zhejiang (8.3%). Hypermucoviscosity and the presence of K1, K2, K20, andrmpAgenes were strongly associated with hvKP (P< 0.001). A significantly higher incidence of liver abscess (P= 0.026), sepsis (P= 0.038), and invasive infections (P= 0.043) was caused by hvKP. Cancer (odds ratio [OR], 2.285) and diabetes mellitus (OR, 2.256) appeared to be independent variables associated with hvKP infections by multivariate analysis. Importantly, 12.6% of hvKP isolates produced ESBLs, and most of them carriedblaCTX-Mgenes. Patients with neutropenia (37.5% versus 5.6%;P= 0.020), history of systemic steroid therapy (37.5% versus 5.6%;P= 0.020), and combination therapy (62.5% versus 16.7%;P= 0.009) were more likely to be infected with ESBL-producing hvKP. The prevalence of hvKP is high in China and has a varied geographic distribution. ESBL-producing hvKP is emerging, suggesting an urgent need to enhance clinical awareness, especially for immunocompromised patients receiving combination therapy.

scholarly journals Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

2016 ◽  
Vol 60 (6) ◽  
pp. 3601-3607 ◽  
Author(s):  
A. Gomez-Simmonds ◽  
B. Nelson ◽  
D. P. Eiras ◽  
A. Loo ◽  
S. G. Jenkins ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Active Agent ◽  
Bloodstream Infections ◽  
Individual Treatment ◽  
Beta Lactam ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum

Previous studies reported decreased mortality in patients with carbapenemase-producingKlebsiella pneumoniaebloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistantK. pneumoniae(CRKP) according to the number ofin vitroactive agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P= 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1;P= 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0;P= 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%,P= 0.1) or BL versus no BL (26% versus 39%,P= 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

scholarly journals Carbapenemase-Producing Klebsiella pneumoniae Bloodstream Infections: Lowering Mortality by Antibiotic Combination Schemes and the Role of Carbapenems

2014 ◽  
Vol 58 (4) ◽  
pp. 2322-2328 ◽  
Author(s):  
George L. Daikos ◽  
Sophia Tsaousi ◽  
Leonidas S. Tzouvelekis ◽  
Ioannis Anyfantis ◽  
Mina Psichogiou ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Active Drug ◽  
Bloodstream Infections ◽  
Definitive Treatment ◽  
Content Type ◽  
Hazards Model ◽  
High Prevalence ◽  
Underlying Diseases

ABSTRACTCarbapenemase-producingKlebsiella pneumoniaestrains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%;P= 0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03;P= 0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08;P< 0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96;P= 0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51;P= 0.006), mostly due to the effectiveness of the carbapenem-containing regimens.

scholarly journals Doripenem MICs andompK36Porin Genotypes of Sequence Type 258, KPC-Producing Klebsiella pneumoniae May Predict Responses to Carbapenem-Colistin Combination Therapy among Patients with Bacteremia

2014 ◽  
Vol 59 (3) ◽  
pp. 1797-1801 ◽  
Author(s):  
Ryan K. Shields ◽  
M. Hong Nguyen ◽  
Brian A. Potoski ◽  
Ellen G. Press ◽  
Liang Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Sequence Type ◽  
Content Type

ABSTRACTTreatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producingKlebsiella pneumoniaewere significantly more likely if both agents were inactivein vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a majorompK36porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134–135 GD], IS5promoter insertion [P= 0.007]) or a doripenem MIC of >8 μg/ml (P= 0.01). MajorompK36mutations among KPC-K. pneumoniaestrains are important determinants of carbapenem-colistin responsesin vitroandin vivo.

scholarly journals Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient

2018 ◽  
Vol 6 (21) ◽  
Author(s):  
Qiong Chen ◽  
Jia-wei Zhou ◽  
Sheng-hai Wu ◽  
Xiao-hua Meng ◽  
Dao-jun Yu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Draft Genome ◽  
Bloodstream Infections ◽  
Mortality Rates ◽  
Resistance Mechanisms ◽  
Severe Problem ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Infection Patient ◽  
Generation Sequencing

ABSTRACT Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The bla KPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing.

scholarly journals Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Willames M. B. S. Martins ◽  
Marisa F. Nicolas ◽  
Yang Yu ◽  
Mei Li ◽  
Priscila Dantas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Illumina Miseq ◽  
Clinical Analysis ◽  
High Copy Number ◽  
Health Concern ◽  
Helper Plasmid ◽  
Content Type

ABSTRACT This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolates were further analyzed by Nanopore MinION sequencing, allowing complete chromosome and plasmid circularization (hybrid assembly), using Unicycler software. The clinical analysis showed that the 30-day overall mortality for these BSI cases was high (83%). The isolates exhibited meropenem resistance (MICs, 32 to 128 mg/liter), with 3/6 isolates resistant to polymyxin B. The conjugative properties of the blaKPC-2 plasmid and its copy number were assessed by standard conjugation experiments and sequence copy number analysis. We identified in all six isolates a small (8.3-kb), high-copy-number (20 copies/cell) non-self-conjugative IncQ plasmid harboring blaKPC-2 in a non-Tn4401 transposon. This plasmid backbone was previously reported to harbor blaKPC-2 only in Brazil, and it could be comobilized at a high frequency (10−4) into Escherichia coli J53 and into several high-risk K. pneumoniae clones (ST258, ST15, and ST101) by a common IncL/M helper plasmid, suggesting the potential of international spread. This study thus identified the international K. pneumoniae ST15 clone as a carrier of blaKPC-2 in a high-copy-number IncQ1 plasmid that is easily transmissible among other common Klebsiella strains. This finding is of concern since IncQ1 plasmids are efficient antimicrobial resistance determinant carriers across Gram-negative species. The spread of such carbapenemase-encoding IncQ1 plasmids should therefore be closely monitored. IMPORTANCE In many parts of the world, carbapenem resistance is a serious public health concern. In Brazil, carbapenem resistance in Enterobacterales is mostly driven by the dissemination of KPC-2-producing K. pneumoniae clones. Despite being endemic in this country, only a few reports providing both clinical and genomic data are available in Brazil, which limit the understanding of the real clinical impact caused by the dissemination of different clones carrying blaKPC-2 in Brazilian hospitals. Although several of these KPC-2-producer K. pneumoniae isolates belong to the clonal complex 258 and carry Tn4401 transposons located on large plasmids, a concomitant emergence and silent dissemination of small high-copy-number blaKPC-2 plasmids are of importance, as described in this study. Our data identify a small high-copy-number IncQ1 KPC plasmid, its clinical relevance, and the potential for conjugative transfer into several K. pneumoniae isolates, belonging to different international lineages, such as ST258, ST101, and ST15.

scholarly journals Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae byIn VitroTime-Kill Experiments

2014 ◽  
Vol 58 (3) ◽  
pp. 1757-1762 ◽  
Author(s):  
T. Tängdén ◽  
R. A. Hickman ◽  
P. Forsberg ◽  
P. Lagerbäck ◽  
C. G. Giske ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Active Drug ◽  
Bactericidal Effect ◽  
Beta Lactamase ◽  
Limited Data ◽  
Content Type ◽  
Bactericidal Effects ◽  
Time Kill

ABSTRACTCombination therapy is recommended for infections with carbapenemase-producingKlebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producingK. pneumoniae(MBL-KP). Two VIM- and two NDM-producingK. pneumoniaestrains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log10decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producingK. pneumoniae. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.

scholarly journals Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae

2016 ◽  
Vol 60 (7) ◽  
pp. 4128-4139 ◽  
Author(s):  
James Albiero ◽  
Sherwin K. B. Sy ◽  
Josmar Mazucheli ◽  
Silvana Martins Caparroz-Assef ◽  
Bruno Buranello Costa ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Clinical Utility ◽  
Multidrug Resistant ◽  
Target Attainment ◽  
Content Type ◽  
Serious Infections ◽  
High Death ◽  
Potential Clinical Utility ◽  
Better Than

ABSTRACTKPC-producingKlebsiella pneumoniaecauses serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producingK. pneumoniae. The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50and MIC90of each agent alone and in combination were challenged against short (1.5-h) or prolonged (3-h) infusion regimens of meropenem (1 g every 8 h [q8h], 1.5 g q6h, 2 g q8h) and fosfomycin (4 g q8h, 6 g q6h, 8 g q8h) by Monte Carlo simulation to evaluate the time above the MIC of the free drug concentration as a percentage of the dosing interval (fT>MIC). The monotherapy MIC50s and MIC90s were 32 and 256 mg/liter for meropenem and 64 and 512 mg/liter for fosfomycin, respectively. Antimicrobial combination increased bacterial susceptibility to 1/4 the MIC50s and to 1/8 to 1/16 the MIC90s of monotherapy. The antimicrobial combination demonstrated a synergistic effect for at least two-thirds of the isolates. In combination therapy, fosfomycin regimens of 6 g q6h and 8 g q8h as a 3-h infusion against the MIC50and MIC90had better chances of achieving ≥90% probability of target attainment (PTA) of 70%fT>MIC. Meropenem regimens of 1.5 g q6h and 2 g q8h in prolonged infusion can achieve close to 90% PTA of 40%fT>MIC for MIC50but not MIC90. The significant reduction in the MIC values and the achievement of appropriate PTA demonstrated that regimens containing fosfomycin with meropenem can be effective against KPC-2-producingK. pneumoniae.

scholarly journals Genomic investigation of a suspected Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Jennifer Cornick ◽  
Patrick Musicha ◽  
Chikondi Peno ◽  
Ezgi Seager ◽  
Pui-Ying Iroh Tam ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Type Species ◽  
Bloodstream Infections ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Link Type ◽  
Sub Saharan ◽  
Neonatal Care Unit ◽  
Suspected Outbreak

A special-care neonatal unit from a large public hospital in Malawi was noted as having more frequent, difficult-to-treat infections, and a suspected outbreak of multi-drug-resistant Klebsiella pneumoniae was investigated using genomic characterisation. All K. pneumoniae bloodstream infections (BSIs) from patients in the neonatal ward (n=62), and a subset of K. pneumoniae BSI isolates (n=38) from other paediatric wards in the hospital, collected over a 4 year period were studied. After whole genome sequencing, the strain sequence types (STs), plasmid types, virulence and resistance genes were identified. One ST340 clone, part of clonal complex 258 (CC258) and an ST that drives hospital outbreaks worldwide, harbouring numerous resistance genes and plasmids, was implicated as the likely cause of the outbreak. This study contributes molecular information necessary for tracking and characterizing this important hospital pathogen in sub-Saharan Africa.

scholarly journals Ten years of population-level genomic Escherichia coli and Klebsiella pneumoniae serotype surveillance informs vaccine development for invasive infections

2020 ◽  
Author(s):  
Samuel Lipworth ◽  
Karina-Doris Vihta ◽  
Kevin K Chau ◽  
James Kavanagh ◽  
Timothy Davies ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vaccine Development ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Population Level ◽  
Small Subset ◽  
Invasive Infections ◽  
Common Serotypes ◽  
O Antigens

The incidence of bloodstream infections (BSIs) caused by Enterobacteriaceae (e.g. Escherichia coli, Klebsiella pneumoniae) continues to increase globally and the threat of untreatable disease is substantial1. Prophylactic vaccines represent an alternative approach to combating antimicrobial resistance (AMR) by reducing antibiotic usage and preventing infections caused by AMR-associated strains. To investigate their potential utility, we performed in silico serotyping on 4035 E. coli/K. pneumoniae BSI from population-level surveillance in Oxfordshire (2008-2018) in addition to 3678 isolates from previous studies. Most infections, including those associated with AMR, were caused by isolates with a small subset of O-antigens, with no evidence that the proportion of BSIs caused by these changed significantly over time. O-antigen targeted vaccines might therefore be useful in reducing the significant morbidity and mortality2 associated with BSIs. Vaccines may also have a role in preventing the spread of carbapenem resistance genes into common serotypes associated with community-onset disease.

Sign in / Sign up

Export Citation Format

Share Document